Article
Biochemistry & Molecular Biology
Kazumi Sakai, Hiroki Ikeuchi, Chihiro Fujiyabu, Yasushi Imamoto, Takahiro Yamashita
Summary: Opsins are universal photoreceptive proteins in animals that play a role in regulating cyclic nucleotide signaling. Different types of opsins in different animals form different active states during photoconversion, and the position of the negatively charged counterion varies. Through analyzing a distinct group of opsins, researchers found that the counterion position change is related to the efficiency of signaling. This study provides insights into the evolutionary process of opsins and their signaling efficiency.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Yann Waltenspuhl, Janosch Ehrenmann, Christoph Klenk, Andreas Pluckthun
Summary: This article summarizes engineering strategies based on directed evolution to reduce workload and enable biophysical experiments of particularly challenging GPCRs.
Review
Endocrinology & Metabolism
Fanhua Wang, Mingyao Liu, Ning Wang, Jian Luo
Summary: This review discusses the role of G-protein coupled receptors (GPCRs) in osteoarthritis (OA), including the pathophysiological processes involved, preclinical and clinical trial data, and the challenges in developing therapies targeting GPCRs for OA.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Cell Biology
Xiaoming Fang, Andrew A. Peden, Fredericus J. M. van Eeden, Jarema J. Malicki
Summary: Opsin plays a crucial role in vertebrate photoreceptors by being transported to the outer segment for its function. Studies have shown that there are differences in the transport mechanisms of opsins in different species, which may be related to changes in amino acid sequences.
JOURNAL OF CELL SCIENCE
(2021)
Article
Biology
Nik Lupse, Monika Klodawska, Veronika Truhlarova, Prokop Kosatko, Vojtech Kaspar, Arnold Roger Bitja Nyom, Zuzana Musilova
Summary: Fish often change their habitat and trophic preferences during development, which also affects their sensory systems, including vision. This study investigates the gene expression profiles of photoreceptors in the retina during development using comparative transcriptomics on 63 fish species. The findings suggest general developmental patterns of opsin expression and reveal specific changes in selected species, providing molecular support for understanding the stage-specific visual features and shifts in fish.
PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Kate F. Byrne, Ajay Pal, James F. Curtin, John C. Stephens, Gemma K. Kinsella
Summary: The focus of the review is on G-protein-coupled receptor (GPCR) targets, with chemokine, cannabinoid, and dopamine receptors showing promise. Further research is needed on potential targets such as MC4R, adhesion receptors, LPA, and Smo receptors to develop new drug-screening strategies for safe and effective GBM therapies.
DRUG DISCOVERY TODAY
(2021)
Review
Biochemistry & Molecular Biology
Dekel David, Ziv Bentulila, Merav Tauber, Yair Ben-Chaim
Summary: GPCRs are involved in signal transduction processes, and although they span the cell membrane, they have not been considered to be regulated by membrane potential. Recent studies, however, have shown that several GPCRs are voltage regulated. This review discusses the advances in understanding the voltage dependence of GPCRs, the suggested molecular mechanisms, and the possible physiological roles.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Andrey V. Struts, Alexander V. Barmasov, Steven D. E. Fried, Kushani S. K. Hewage, Suchithranga M. D. C. Perera, Michael F. Brown
Summary: This article summarizes and reviews the osmotic stress studies of G-protein-coupled receptor rhodopsin. It is found that water plays an important role in the activation of the receptor, with at least 80 water molecules entering the receptor in the transition to the active state. If water influx is prevented, the functional transition of the receptor is reversed. These findings reveal the phenomenon of solvent swelling in the activation mechanism of rhodopsin, with water acting as an allosteric modulator of function for rhodopsin-like receptors in lipid membranes.
BIOPHYSICAL CHEMISTRY
(2024)
Article
Biology
Ramon Cierco Jimenez, Nil Casajuana-Martin, Adrian Garcia-Recio, Lidia Alcantara, Leonardo Pardo, Mercedes Campillo, Angel Gonzalez
Summary: The study analyzed 119,069 natural variants in human olfactory receptors, revealing a significant diversity of natural variations in the olfactory gene repertoire between individuals and populations, with a considerable number of changes occurring at the structurally conserved regions. Mutations in positions linked to the conserved GPCR activation mechanism were highlighted, which could imply phenotypic variation in olfactory perception.
Review
Pharmacology & Pharmacy
Sergi Ferre, Francisco Ciruela, Carmen W. Dessauer, Javier Gonzalez-Maeso, Terence E. Hebert, Ralf Jockers, Diomedes E. Logothetis, Leonardo Pardo
Summary: The study proposes the concept of GPCR-effect assemblies (GEMMAs), which are pre-assembled before receptor activation and allow more efficient interactions between specific signaling components. This offers an alternative model to the conventional collision coupling model and explains the differential properties of GPCRs in different cellular environments.
PHARMACOLOGY & THERAPEUTICS
(2022)
Review
Chemistry, Multidisciplinary
Xin-heng He, Chong-zhao You, Hua-liang Jiang, Yi Jiang, H. Eric Xu, Xi Cheng
Summary: G protein-coupled receptors (GPCRs) are important drug targets that play crucial roles in various physiological processes. Although extensive efforts have been made in the field of structural biology, a significant number of GPCR structures remain unsolved due to their structural instability. Recently, AlphaFold2 has been developed as a tool to predict the structure models of GPCRs and other functionally important proteins. However, our evaluation reveals several differences between the predicted models and experimental structures, such as the assembly of domains, shape of ligand-binding pockets, and conformation of binding interfaces. These differences hinder the use of predicted structure models in functional studies and structure-based drug design, where reliable high-resolution structural information is required.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Biochemistry & Molecular Biology
Wojciech Pietrus, Rafal Kurczab, Dagmar Stumpfe, Andrzej J. Bojarski, Juergen Bajorath
Summary: The study showed that introducing fluorine can significantly increase ligand potency, but the effect of fluorination on affinity varies depending on the fluorination position. Fluorination of the aromatic ring at the ortho position is favorable for potency enhancement, while fluorination of aliphatic fragments more often leads to a decrease in biological activity.
Article
Biochemistry & Molecular Biology
Naoya Morimoto, Takashi Nagata, Keiichi Inoue
Summary: This study revealed that human and chicken RGRs form blue-absorbing pigments similar to bovine RGR, and they are bistable rhodopsins displaying a reversible photoreaction. These findings provide insight into the behavior of RGR as a retinal photoisomerase and aid in understanding its role in the visual system.
Article
Chemistry, Multidisciplinary
Yunfang Xiong, Ran Ke, Qingyu Zhang, Wenjun Lan, Wanjun Yuan, Karol Nga Ieng Chan, Tom Roussel, Yifan Jiang, Jing Wu, Shuai Liu, Alice Sze Tsai Wong, Joong Sup Shim, Xuanjun Zhang, Ruiyu Xie, Nelson Dusetti, Juan Iovanna, Nagy Habib, Ling Peng, Leo Tsz On Lee
Summary: This study reports the effective modulation of a GPCR for cancer treatment using small activating RNAs (saRNAs) for the first time. The saRNAs promote the expression of MAS1, a GPCR that counteracts cancer cell proliferation and migration. By enhancing MAS1 expression, these saRNAs suppress tumorigenesis and inhibit tumor progression in multiple cancer models. This research not only provides a new strategy for cancer therapy by targeting the renin-angiotensin system, but also offers a new avenue to modulate GPCR signaling through RNA activation.
Review
Engineering, Biomedical
Yuhong Jiang, Yuke Li, Xiujuan Fu, Yue Wu, Rujing Wang, Mengnan Zhao, Canquan Mao, Sanjun Shi
Summary: The translation article introduces the interaction between G protein-coupled receptors (GPCRs) and nanotechnology, as well as how nanotechnology can improve the efficacy and safety of GPCR-related drugs. Nanotechnology can encapsulate GPCR ligands to construct synthetic nano-GPCRs and precisely initiate sustained endosomal signal transduction through nanoparticles. Moreover, nanoparticles can enhance the potency of delivery systems by actively targeting specific cells through ligand-receptor binding and receptor-dependent endocytosis.
ACTA BIOMATERIALIA
(2023)
Article
Biochemistry & Molecular Biology
Diane C. A. Barret, Gebhard F. X. Schertler, U. Benjamin Kaupp, Jacopo Marino
Summary: The cryo-EM structure of the bovine rod CNG channel isolated from retina reveals an additional gate within the ion conduction pathway contributed by the CNGB1 subunit, shedding light onto the structural basis and answering long-standing questions regarding the function of CNG channels in visual and olfactory neurons.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Article
Chemistry, Physical
Cecilia M. Casadei, Ahmad Hosseinizadeh, Gebhard F. X. Schertler, Abbas Ourmazd, Robin Santra
Summary: Time-resolved serial femtosecond crystallography (TR-SFX) allows for the study of protein dynamics with atomic resolution on sub-picosecond timescales. In this work, the authors propose a novel approach called low-pass spectral analysis (LPSA) to improve the analysis of TR-SFX data. LPSA projects the data onto a subspace defined by trigonometric functions, attenuating high-frequency features and facilitating the retrieval of underlying dynamics. The authors demonstrate the effectiveness of LPSA in reconstructing dynamics and compare it to other existing data analysis techniques.
STRUCTURAL DYNAMICS-US
(2022)
Article
Biochemistry & Molecular Biology
Jessica Rodgers, Steven Hughes, Moritz Lindner, Annette E. Allen, Aghileh S. Ebrahimi, Riccardo Storchi, Stuart N. Peirson, Robert J. Lucas, Mark W. Hankins
Summary: Photoreceptor degeneration can lead to severe visual loss but often spares the inner retina, providing hope for vision restoration treatments using optogenetics or electrical stimulation. In a mouse model, the optogenetic actuator ReaChR was found to generate a visual code similar to the wild-type, indicating the impressive ability of surviving circuitry to recreate a rich visual code following retinal degeneration. These findings have important implications for regenerative medicine in the central nervous system.
Review
Endocrinology & Metabolism
Brian P. Cary, Xin Zhang, Jianjun Cao, Rachel M. Johnson, Sarah J. Piper, Elliot J. Gerrard, Denise Wootten, Patrick M. Sexton
Summary: G protein-coupled receptors (GPCRs), particularly the B1 class, play a critical role in maintaining homeostasis and are important drug targets. Recent advances in cryo-electron microscopy have provided valuable insights into the structure and dynamics of these receptors, which contribute to our understanding of their functions.
Article
Biochemistry & Molecular Biology
Shunpei Hanai, Takashi Nagata, Kota Katayama, Shino Inukai, Mitsumasa Koyanagi, Keiichi Inoue, Akihisa Terakita, Hideki Kandori
Summary: Animal visual rhodopsins can be classified into monostable and bistable rhodopsins, typically found in vertebrates and invertebrates respectively. Bovine rhodopsin (BovRh) is an example of monostable rhodopsin with extensively studied structures and functions. On the other hand, the structures and functions of bistable rhodopsins, despite their importance in optogenetics, are less known. In this study, low-temperature Fourier transform infrared (FTIR) spectroscopy was used to compare the spectral changes of jumping spider rhodopsin-1 (SpiRh1), squid rhodopsin (SquRh), and BovRh. The analysis showed that while the chromophore distortion in the resting state is not distinctive between invertebrate and vertebrate rhodopsins, the distortion after photoisomerization is unique for BovRh. Moreover, the analysis of O-D stretching vibrations revealed unique features of protein-bound water molecules. The absence of strongly hydrogen-bonded water molecules is a distinct characteristic of animal rhodopsins compared to microbial rhodopsins.
Article
Biochemistry & Molecular Biology
Naoya Morimoto, Takashi Nagata, Keiichi Inoue
Summary: This study revealed that human and chicken RGRs form blue-absorbing pigments similar to bovine RGR, and they are bistable rhodopsins displaying a reversible photoreaction. These findings provide insight into the behavior of RGR as a retinal photoisomerase and aid in understanding its role in the visual system.
Article
Multidisciplinary Sciences
Ariel Chazan, Ishita Das, Takayoshi Fujiwara, Shunya Murakoshi, Andrey Rozenberg, Ana Molina-Marquez, Fumiya K. Sano, Tatsuki Tanaka, Patricia Gomez-Villegas, Shirley Larom, Alina Pushkarev, Partha Malakar, Masumi Hasegawa, Yuya Tsukamoto, Tomohiro Ishizuka, Masae Konno, Takashi Nagata, Yosuke Mizuno, Kota Katayama, Rei Abe-Yoshizumi, Sanford Ruhman, Keiichi Inoue, Hideki Kandori, Rosa Leon, Wataru Shihoya, Susumu Yoshizawa, Mordechai Sheves, Osamu Nureki, Oded Beja
Summary: Light-harvesting carotenoids, such as zeaxanthin and lutein, transfer energy to the retinal chromophore of xanthorhodopsins and proteorhodopsins, indicating their potential role in rhodopsin phototrophy in lakes, seas, and oceans.
Article
Multidisciplinary Sciences
Diane C. A. Barret, Dina Schuster, Matthew J. Rodrigues, Alexander Leitner, Paola Picotti, Gebhard F. X. Schertler, U. Benjamin Kaupp, Volodymyr M. Korkhov, Jacopo Marino
Summary: Calmodulin (CaM) regulates ion channels to control calcium entry into cells, and mutations affecting this interaction are linked to fatal diseases. The structural basis of CaM regulation is not well understood. In retinal photoreceptors, CaM binds to the CNGB subunit of CNG channels and modulates the channel's sensitivity to changes in ambient light. This study provides the structural characterization of CaM regulation of a CNG channel using cryo-electron microscopy and proteomics.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Kazuaki Yamaguchi, Mitsumasa Koyanagi, Keiichi Sato, Akihisa Terakita, Shigehiro Kuraku
Summary: The 'blue-shifted' visual pigment (RHO) of whale sharks, which adapts them to the deep-sea environment, is mainly caused by an unprecedented spectral tuning at site 94. This study has significant implications for the understanding of visual ecology in deep-diving species.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Brian P. Cary, Elliot J. Gerrard, Matthew J. Belousoff, Madeleine M. Fletcher, Yan Jiang, Isabella C. Russell, Sarah J. Piper, Denise Wootten, Patrick M. Sexton
Summary: This study describes the cryo-EM structures of PTH1R in complex with different agonists, such as PTH, PTH-related protein, abaloparatide, long-acting PTH, and truncated peptide M-PTH(1-14). The N terminus of each agonist engages the transmembrane bundle in a similar way, leading to Gas activation. The full-length peptides induce subtle differences in the orientation of the extracellular domain, while in the structure bound to M-PTH, the extracellular domain remains unresolved, indicating its high dynamic nature in the absence of peptides. Water molecules near peptide and G protein binding sites were also identified. These results provide insights into the mechanism of action of orthosteric agonists of PTH1R.
Article
Biochemical Research Methods
Matthew J. Rodrigues, Cecilia M. Casadei, Tobias Weinert, Valerie Panneels, Gebhard F. X. Schertler
Summary: Rhodopsin is a light-sensitive G-protein-coupled receptor that plays a crucial role in vertebrate vision. By using serial femtosecond crystallography, the structure of rhodopsin was successfully solved at room temperature. However, a lattice-translocation defect (LTD) was discovered in the crystals, which required correction to accurately interpret the data. This correction was essential in order to confidently model the unilluminated state of the receptor and analyze the light-activated data.
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2023)
Article
Chemistry, Physical
Cecilia M. Casadei, Ahmad Hosseinizadeh, Spencer Bliven, Tobias Weinert, Jorg Standfuss, Russell Fung, Gebhard F. X. Schertler, Robin Santra
Summary: Low-pass spectral analysis (LPSA) is an effective algorithm for retrieving dynamics in model data affected by incompleteness and weighting errors. In this study, LPSA is applied to experimental time-resolved crystallography data and the parametric sensitivity is analyzed. The presence of high-frequency contamination in dynamical modes is investigated using synthetic data with various uncertainties and errors. A method is proposed to handle missing observations and improved dynamics retrieval is achieved.
STRUCTURAL DYNAMICS-US
(2023)
Article
Neurosciences
Patrycja Orlowska-Feuer, Beatriz Bano-Otalora, Jessica Rodgers, Franck P. Martial, Riccardo Storchi, Robert James Lucas
Summary: This study investigates how neurons in the main circadian oscillator of the brain respond to changes in light irradiance. The researchers found that the response of individual neurons to irradiance is monotonic but varies in terms of the range of irradiance and the direction of the response.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Biology
Hanako Hagio, Wataru Koyama, Shiori Hosaka, Aysenur Deniz Song, Janchiv Narantsatsral, Koji Matsuda, Tomohiro Sugihara, Takashi Shimizu, Mitsumasa Koyanagi, Akihisa Terakita, Masahiko Hibi, Suresh Jesuthasan
Summary: We examined the functionality of animal G-protein-coupled bistable rhodopsins in zebrafish by controlling them into active and inactive states using light application. The Gq-coupled spider Rh1 expressed in hindbrain reticulospinal V2a neurons increased intracellular Ca2+ levels and induced swimming behavior upon light stimulation. The Gi/o-coupled mosquito Opn3, pufferfish TMT opsin, or lamprey parapinopsin expressed in cardiomyocytes caused cardiac arrest, which could be suppressed by pertussis toxin or barium treatment, indicating the regulation of cardiac function by Gi/o-dependent inward-rectifier K+ channels. These rhodopsins are valuable tools for optogenetic control of GPCR-mediated signaling in zebrafish neurons and cardiomyocytes.
